On-column N-dearylation of 2-azetidinones by silica-supported ceric ammonium nitrate Maaroof Zarei a , Aliasghar Jarrahpour b, * , Edris Ebrahimi b , Malihe Aye b , Seid Ali Torabi Badrabady b a Department of Chemistry, College of Sciences, Hormozgan University, Bandar Abbas 71961, Iran b Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran article info Article history: Received 13 February 2012 Received in revised form 5 April 2012 Accepted 23 April 2012 Available online 30 April 2012 Keywords: On-column reaction N-Dearylation N-Unsubstituted 2-azetidinone b-Lactam Ceric ammonium nitrate Silica-supported abstract A modified traditional preparative chromatographic column can be used to achieve quantitative N- dearylation of N-(alkoxyphenyl), N-(alkoxynaphthyl), and N-(alkoxybenzyl)-2-azetidinones under mild conditions. Starting materials are charged on top of the column and the pure N-unsubstituted 2- azetidinones leave the column minutes later without need for other purifications. The yields are good- to-excellent and the reaction condition is mild, easy, efficient, and cheap. Ó 2012 Elsevier Ltd. All rights reserved. 1. Introduction Ceric ammonium nitrate (CAN) is a one-electron oxidant with advantages, such as low toxicity, ease of handling, and solubility in a number of organic solvents. 1 Ceric ammonium nitrate has proved to be very useful to synthetic organic chemists for several decades. The enormous growth in the use of this reagent is evidenced by the publication of a large number of research papers and several re- views concerning CAN-mediated reactions. 1,2 2-Azetidinones, commonly known as b-lactams, are heterocy- clic compounds well known to organic and medicinal chemists. 3 The activities of widely used antibiotics, such as penicillins, ceph- alosporins, carbapenems, monobactams, and nocardicins are at- tributed to the presence of 2-azetidinone ring. 4 Ezetimibe is a new drug, which has the 2-azetidinone skeleton and selectively inhibits the absorption of cholesterol. 5 Besides the antibacterial and cho- lesterol absorption inhibitory activities, b-lactams possess various other biological activities. 6 b-Lactams are not only useful in me- dicinal applications, but are also used as intermediates and synthon for the production of several organic compounds. 7 Several syn- thetic methods have been developed for the preparation of the b- lactam ring. 8 N-Unsubstituted 2-azetidinones offer major synthetic opportu- nities in the synthesis of b-lactam antibiotics and the glutamine synthetase inhibitor, tabtoxin. 9 Application of N-unsubstituted 2- azetidinones in the semi-synthesis of the anticancer agents Taxol and Taxotere has been also reported. 10 Routes to N-unsubstituted 2-azetidinones involve the reaction of N-trimethylsilyl imines with the corresponding compounds, 11 reaction of chlorosulfonyl isocyanate with alkenes 12 and N- deprotection of N-functionalized b-lactams. Several groups are often used for N-protection of b-lactams and can be deprotected in different methods to give N-unsubstituted b-lactams. 13 With few exceptions the yields are poor. Furthermore some methods need expensive and unavailable materials. Toxic and non-safe byproducts obtained in some cases together with difficulties of the purification of main products are other problems of these methods. Among these methods, oxidative cleavage by ceric ammonium nitrate of p-alkoxyphenyl moiety attached to the ni- trogen of the b-lactam ring offers the most direct synthesis of N- unsubstituted b-lactams. 14 This reaction commonly is performed in aqueous acetonitrile and involves oxidation of the aromatic ring to benzoquinone with the release of 1 mol equiv of corre- sponding alcohol and 1 mol equiv of the cyclic amide (Scheme 1). The mechanism of this reaction has been reported by several groups. 14g,15 Alumina, silica, and clays are of the most widely employed supports, where surface hydroxyl groups play a major role in these reactions. Amongst them silica is widely used as a supporting material since it presents desirable properties and silica gel plays an important role in fine organic synthesis. 14g,16 * Corresponding author. Tel.: þ98 711 228 4822; fax: þ98 711 228 0926; e-mail addresses: jarrah@susc.ac.ir , aliasghar6683@yahoo.com (A. Jarrahpour). Contents lists available at SciVerse ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2012.04.088 Tetrahedron 68 (2012) 5505e5512